Neurodegenerative diseases plague a large number of individuals world wide. For example, an estimated 3-4 million people in the US have Parkinson's disease (PD), which is a chronic progressive neurodegenerative disease that occurs when dopaminergic neurons in the substantia nigra pars compacta of the midbrain degenerate, causing resting tremor, rigidity, and bradykinesia. Currently, there is no cure or definitive means to stop the progression of many neurodegenerative diseases and PD is just one example. However, medications and surgery can relieve many of the symptoms. Such treatments for PD have been developed based on an improved understanding of basal ganglia (BG) anatomy and physiology.
It has been long appreciated that PD follows the degeneration of dopaminergic neurons in the substantia nigra pars compacta. This triggers a cascade of functional changes in the BG that leads to abnormal activity in its output nuclei, the substantia nigra reticulata and globus pallidus internus. Therefore, the goal of traditional treatment is to enhance concentrations of dopamine, or to modify the activity of the output nuclei by creating lesions in target areas, or more recently by using deep brain stimulation (DBS).
DBS is a surgical procedure in which a stimulating probe is implanted in a targeted area, typically the subthalamic nucleus (STN), which is connected to an insulated wire that is passed under the skin of the head, neck, and shoulder and terminated at a neurostimulator, which typically sits inferior to the clavicle. At major surgical centers the surgery has become routine. Patient's motor symptoms generally decrease with treatment and they can regain quality of life and reduce their medications, which have serious side effects.
While traditional DBS is a valuable tool for treating neurological disorders, the stimulation signal must be optimized post-operatively. FIG. 1 provides schematic depiction of the “open loop” feedback system of traditional DBS systems, in which both natural external stimulus x(t) and an administered DBS signal u(t) affect the neuronal activity y(t) of a target region in a subject's brain. The neuronal activity y(t) in turn affects the behavior b(t) of the subject's body, which feeds back to affect the target region. The DBS system is not responsive to feedback from either y(t) or b(t). Therefore, identification of a stimulation signal u(t) that elicits an appropriate subject response is achieved by a manual calibration process in which a multitude of different stimulation signals are evaluated by trial-and-error. Manual calibration is costly in terms of medical resources and can limit the number of patients that a neurologist may treat simultaneously. Calibration can take several weeks or months, during which the high expectations of the subject having an implanted DBS system may not be met, thereby leading to subject depression and medication use. Moreover, current DBS waveforms are high-frequency and can leak into neighboring brain areas, causing side effects. Beyond such undesirable side effects, current DBS systems, employing high-frequency stimulation waveforms, consume significant amounts of power and rapidly drain batteries that must be replaced surgically.
It would therefore be desirable to have DBS system that would reduce the resources needed for calibration and operation and provide more immediate and effective treatment to the patient. Such a system would improve patient care, reduce medical costs, increase the number of patients that a neurologist may treat simultaneously, and improve the performance characteristics, for example, battery life, of the device.